Remote ischemic periconditioning suppresses cardiac sympathetic activation in acute myocardial infarction: a randomized controlled trial.

PURPOSE: Remote ischemic periconditioning (RIPC) has demonstrated cardioprotective effects and improved clinical outcomes as an adjunct to emergent percutaneous coronary intervention (PCI) in patients with ST-elevation myocardial infarction (STEMI). However, whether RIPC affects the cardiac sympathetic nerve activity in patients with STEMI remains unclear. This study investigated the effects of RIPC on cardiac sympathetic nerve activity in patients with STEMI. METHODS: We prospectively assigned patients with STEMI who underwent emergent PCI to receive RIPC or no procedure (control group) upon arrival at the cardiac catheterization laboratory. The primary endpoint was cardiac sympathetic nerve activity assessed through the washout rate (WR) in cardiac 123I-metaiodobenzylguanidine (123I-MIBG) imaging. RESULTS: Patients in the RIPC (n = 62) and control (n = 60) groups had similar demographic and clinical characteristics at baseline. Multivariable linear regression models revealed that the culprit lesion of the left anterior descending artery and hemoglobin level were significantly and independently associated with WR at discharge. WRs of the groups differed insignificantly at discharge. However, the RIPC group (n = 49) showed significantly lower WR than the control group (n = 47) at 1 year after discharge (p = 0.027). In the single-photon emission computed tomography analysis at 1 year after discharge, the RIPC group demonstrated significantly higher late uptake (p = 0.021) and lower WR (p = 0.013) in the nonculprit lesion, with a non-significant decrease in WR for the culprit lesion. CONCLUSION: RIPC can suppress augmented cardiac sympathetic nerve activity in patients with STEMI, particularly in nonculprit lesions.

Uptitration of Sacubitril/Valsartan and Outcomes in Patients With Heart Failure　- Insight From the REVIEW-HF Registry.

BACKGROUND: Guideline-directed medical therapy has become an important component of heart failure (HF) therapy, with sacubitril/valsartan as one of the recommended drugs; however, the real-world prognostic implications of sacubitril/valsartan uptitration are unclear. METHODS AND RESULTS: Patients with HF newly initiated on sacubitril/valsartan were registered in a retrospective multicenter study (REVIEW-HF). In all, 995 patients were divided into 3 groups according to the maximum dose achieved: high dose, sacubitril/valsartan 400 mg; intermediate dose, sacubitril/valsartan 200-<400 mg; and low dose, sacubitril/valsartan <200 mg. A total of 397 (39.9%) patients received high-dose sacubitril/valsartan; they had a significantly lower risk of mortality or HF hospitalization than patients in the low-dose (hazard ratio [HR] 0.39; 95% confidence interval [CI] 0.29-0.53; P<0.001) and intermediate-dose (HR 0.64; 95% CI 0.45-0.94; P=0.03) groups. In the multivariable Cox regression model, higher systolic blood pressure and maintained geriatric nutritional risk index were significantly associated with a higher incidence of achieving a high dose of sacubitril/valsartan. Patients who did not receive high-dose sacubitril/valsartan experienced more hypotension during the follow-up period, whereas hyperkalemia, severe renal events, and angioedema did not differ across the achieved dose classifications. CONCLUSIONS: Patients who achieved sacubitril/valsartan uptitration had a better prognosis than those who did not. Before sacubitril/valsartan uptitration, patients need to monitor blood pressure closely to prevent worsening events.

A systematic approach for transcatheter mitral valve edge-to-edge repair of isolated commissure prolapse.

Although transcatheter mitral valve edge-to-edge repair (TEER) has been widely used for non-central degenerative mitral regurgitation (MR), few reports have described therapeutic strategies for commissure prolapse. Furthermore, no standard approach for TEER for commissure has established. Thus, we categorized various grasping strategies into three patterns, and proposed a promising systematic strategy to observe three possible grasping patterns for identifying appropriate grasping target. Here, we report a successful TEER case of isolated posterior commissure prolapse in which we used a systematic approach.

Usefulness of the 2-year iodine-123 metaiodobenzylguanidine-based risk model for post-discharge risk stratification of patients with acute decompensated heart failure.

PURPOSE: A four-parameter risk model that included cardiac iodine-123 metaiodobenzylguanidine (MIBG) imaging and readily available clinical parameters was recently developed for prediction of 2-year cardiac mortality risk in patients with chronic heart failure. We sought to validate the ability of this risk model to predict post-discharge clinical outcomes in patients with acute decompensated heart failure (ADHF) and to compare its prognostic value with that of the Acute Decompensated Heart Failure National Registry (ADHERE) and Get With The Guidelines-Heart Failure (GWTG-HF) risk scores. METHODS: We studied 407 consecutive patients who were admitted for ADHF and survived to discharge, with definitive 2-year outcomes (death or survival). Cardiac MIBG imaging was performed just before discharge. The 2-year cardiac mortality risk was calculated using four parameters, namely age, left ventricular ejection fraction, New York Heart Association functional class, and cardiac MIBG heart-to-mediastinum ratio on delayed images. Patients were stratified into three groups based on the 2-year cardiac mortality risk: low- (< 4%), intermediate- (4-12%), and high-risk (> 12%) groups. The ADHERE and GWTG-HF risk scores were also calculated. RESULTS: There was a significant difference in the incidence of cardiac death among the three groups stratified using the 2-year cardiac mortality risk model (p < 0.0001). The 2-year cardiac mortality risk model had a higher C-statistic (0.732) for the prediction of cardiac mortality than the ADHERE and GWTG-HF risk scores. CONCLUSION: The 2-year MIBG-based cardiac mortality risk model is useful for predicting post-discharge clinical outcomes in patients with ADHF. TRIAL REGISTRATION NUMBER: UMIN000015246, 25 September 2014.

Prediction of sudden cardiac death in chronic heart failure patients with reduced ejection fraction by ADMIRE-HF risk score and early repolarization pattern.

BACKGROUND: AdreView myocardial imaging for risk evaluation in heart failure (ADMIRE-HF) risk score is a novel risk score to predict serious arrhythmic risk in chronic heart failure patients with reduced ejection fraction (HFrEF). Moreover, early repolarization pattern (ERP) has been shown to be associated with an increased risk of sudden cardiac death (SCD) in HFrEF patients. We sought to investigate the prognostic value of combining ADMIRE-HF risk score and ERP to predict SCD in HFrEF patients. METHODS: We studied 90 HFrEF outpatients with LVEF< 40% in our prospective cohort study. In cardiac MIBG imaging, the heart-to-mediastinum (H/M) ratio was measured on the delayed planar image. ADMIRE-HF risk score was derived from the sum of the point values of LVEF, H/M ratio, and systolic blood pressure. We also assessed ERP on the standard electrocardiogram. RESULTS: During a median follow-up of 7.5(4.5-12.0) years, 22 patients had SCD. At multivariate Cox analysis, ADMIRE-HF risk score and ERP were independently associated with SCD. Patients with both intermediate/high ADMIRE-HF score and ERP had a higher SCD risk than those with either and none of them. CONCLUSION: The combination of ADMIRE-HF risk score and ERP would provide the incremental prognostic information for predicting SCD in HFrEF patients.

Prediction of sudden cardiac death in patients with chronic heart failure by regional washout rate in cardiac MIBG SPECT imaging.

BACKGROUND: The sympathetic nervous system provides an important trigger for major arrhythmic events through regional heterogeneity of sympathetic activity, which could be evaluated by SPECT imaging as the regional MIBG washout rate (WR). There is little information available on the prognostic value of regional WR in SPECT imaging for the prediction of sudden cardiac death (SCD) in patients with chronic heart failure (CHF). METHODS: We studied 73 CHF outpatients with LVEF < 40%. At study entry, the regional WR was measured in 17 segments on the polar map. We defined abnormal regional WR as both the regional WR range (maximum - minimum regional WR) and maximum regional WR > mean value + 2SD obtained in 15 normal controls. RESULTS: During a mean follow-up of 7.5 ± 4.1 years, 15 of 73 patients had SCD. The abnormal regional WR and abnormal global WR on planar images were significantly and independently associated with SCD. Patients with both the abnormal regional WR and global WR had a significantly higher risk of SCD than those with none of these criteria. CONCLUSIONS: The analysis of regional MIBG WR on SPECT imaging provides additional prognostic value to global WR on planar images for SCD prediction in CHF patients.

Cryptococcus endocarditis: A case report and review of the literature.

INTRODUCTION: Cryptococcus neoformans is known to be a cause of meningitis. However, as cryptococcal endocarditis is rare, it is not well understood. Here, we describe a case with Implantable Cardioverter Defibrillator associated endocarditis and meningitis caused by Cryptococcus neoformans and we review the literature associated cryptococcal endocarditis. CASE PRESENTATION: A 72 years old Japanese male presented in emergency department with non-productive cough and respiratory discomfort. His past medical history was ischemic heart disease four years ago and ICD was implanted. Physical examination was unremarkable. Chest computer tomography revealed ground glass opacity in the right lung. He received a diagnosis of amiodarone-induced interstitial pneumonitis and high dose steroid pulse therapy. Septic shock and acute respiratory failure occurred after steroid therapy. Cryptococcus neoformans was identified by blood culture and cerebral spinal fluid. Intravenous liposomal Amphotericin B and oral flucytosine were initiated. Transesophageal echocardiography revealed vegetation on the lead of the ICD. Diagnosis of cryptococcal endocarditis was made. The patient died despite antifungal therapy was continued. DISCUSSION: We analyzed our case and 8 cases of cryptococcal endocarditis in the literature for 40 years. Almost all of the patients had previous valve replacement surgery or immunocompromised state. Three cases had meningitis. Surgery performed in 3 cases. The overall mortality rate were 44.4%. CONCLUSIONS: Cryptococcal endocarditis is rare and carries a high mortality. Almost all of the patients had underlying diseases. Diagnosis needs repeating blood culture and echocardiogram, sometimes. Cryptococcal endocarditis needs lumber puncture for rule out meningitis.

Serial Change in Serum Chloride During Hospitalization Could Predict Heart Failure Death in Acute Decompensated Heart Failure Patients.

BACKGROUND: Although hyponatremia predicts morbidity and mortality in acute decompensated heart failure (ADHF), hypochloremia is also independently associated with poor prognosis in ADHF. Little is known, however, about the prognostic value of serial change in serum chloride during hospitalization in ADHF patients.Methods and Results:We prospectively studied 208 ADHF survivors after discharge and divided them into 4 groups according to serum chloride on admission and at discharge: (1) persistent hypochloremia group (n=12), hypochloremia both on admission and at discharge; (2) progressive hypochloremia group (n=42), development of hypochloremia after admission; (3) improved hypochloremia group (n=14), hypochloremia only on admission; and (4) no hypochloremia group, no hypochloremia during hospitalization (n=140). During a mean follow-up period of 1.86±0.76 years, 20 of 208 patients had heart failure death (HFD). In a model adjusted for hyponatremia, hypochloremia both on admission and at discharge was still significantly associated with HFD. Hyponatremia, however, was not significantly associated with HFD after adjustment for hypochloremia. Patients with persistent hypochloremia (HR, 9.13; 95% CI: 2.56-32.55) and with progressive hypochloremia (HR, 4.65; 95% CI: 1.61-13.4) had a significantly greater risk of HFD than those without hypochloremia during hospitalization. CONCLUSIONS: Both persistent hypochloremia and progressive hypochloremia during hospitalization are associated with HFD in ADHF patients.

Tolvaptan Reduces the Risk of Worsening Renal Function in Patients With Acute Decompensated Heart Failure and Preserved Left Ventricular Ejection Fraction　- Prospective Randomized Controlled Study.

BACKGROUND: Although the mainstay of treatment for acute decompensated heart failure (ADHF) is decongestion by diuretic therapy, it is often associated with worsening renal function (WRF). The effect of tolvaptan, a selective V2 receptor antagonist, on WRF in ADHF patients with preserved left ventricular ejection fraction (LVEF) is unknown.Methods and Results:We enrolled 50 consecutive ADHF patients whose LVEF on admission was ≥45%. Patients were randomly assigned to either tolvaptan add-on (n=26) or conventional diuretic therapy (n=24). The primary endpoint was the incidence of WRF, defined as an increase in serum creatinine (Cr) ≥0.3 mg/dL or 50% above baseline within 48 h of randomization. There was no significant difference between the 2 groups in the change in body weight or the total urine volume during 48 h. However, the change in Cr (∆Cr) at 24 and 48 h after randomization and the incidence of WRF (12% vs. 42%, P=0.0236) were significantly lower, and the fractional excretion of urea (FEUN) at 24 and 48 h after randomization was significantly higher in the tolvaptan group. There was an inverse correlation between ∆Cr and FEUN at 48 h after randomization. CONCLUSIONS: Tolvaptan can alleviate congestion with a significantly lower risk of WRF in ADHF patients with preserved LVEF, presumably through maintenance of renal perfusion.

Eplerenone might affect atrial fibrosis in patients with hypertension.

BACKGROUND: Eplerenone is reported to reduce the development of atrial fibrillation (AF). The aim of this study was to clarify the mechanism of eplerenone for AF prevention from the viewpoint of P wave morphology, which is reported to correlate with atrial fibrosis. METHODS: Thirty-five patients with hypertension, who were randomized to receive eplerenone (n = 16) or amlodipine (n = 19) for 1 year, were evaluated. P wave signal-averaged electrocardiography was recorded at baseline and 1 year after entry, and P wave duration (Ad) and P wave dispersion (P-disp) were obtained. Serum levels of intact procollagen type I N-terminal propeptide (PINP) and N-terminal procollagen-III peptide (PIIIP) were also measured. RESULTS: There were no significant differences in baseline clinical characteristics including Ad, P-disp, and the decrease in blood pressure at 1-year follow-up between the two groups. Ad and P-disp (mean ± standard deviation) significantly increased in patients on amlodipine after 1 year (140 ± 21 ms to 139 ± 19 ms vs 132 ± 10 ms to 136 ± 12 ms, P < 0.01 and 14 ± 7 ms to 9 ± 4 ms vs 12 ± 5 to 16 ± 8, P < 0.01, respectively). PINP was significantly more decreased in patients with eplerenone than amlodipine (56.6 ± 30.4 µg/mL to 46.6 ± 19.4 µg/mL vs 41.5 ± 16.2 µg/L to 48.7 ± 21.3 µg/L, P < 0.01). Percent changes of Ad, P-disp, PINP, and PIIIP were significantly smaller in patients with eplerenone than amlodipine (0.0 ± 4.7% vs 3.2 ± 4.4%, P < 0.05, - 28.6 ± 31.0% vs 46.3 ± 73.0%, P < 0.01, - 5.6 ± 38.1% vs 22.7 ± 42.7%, P < 0.05, and - 9.2 ± 25.1% vs 7.4 ± 19.0%, P < 0.05, respectively). CONCLUSIONS: Eplerenone reduced the increase of Ad and P-disp with a decrease of PINP and PIIIP, which might translate into reduction of atrial fibrosis. This study showed that eplerenone may be useful as upstream therapy for AF in patients with hypertension.

The CHADS2 score predicts ischemic stroke in chronic heart failure patients without atrial fibrillation: comparison to other stroke risk scores.

The CHADS2 score is useful in stratifying the risk of ischemic stroke or transient ischemic attack (TIA) in patients with non-valvular atrial fibrillation (AF). However, it remains unclear whether the CHADS2 score could predict stroke or TIA in chronic heart failure (CHF) patients without AF. Recently, the new stroke risk score was proposed from 2 contemporary heart failure trials. We evaluated the prognostic power of the CHADS2 score for stroke or TIA in CHF patients without AF in comparison to the "stroke risk score". We retrospectively studied 127 CHF patients [left ventricular ejection fraction (LVEF) <40 %] without AF, who had been enrolled in our previous prospective cohort study. The primary endpoint was the incidence of stroke or TIA. The mean baseline CHADS2 score was 2.1 ± 1.0. During the follow-up period of 8.4 ± 5.1 years, stroke or TIA occurred in 21 of 127 patients. At multivariate Cox analysis, CHADS2 score (C-index 0.794), but not "stroke risk score" (C-index 0.625), was significantly and independently associated with stroke or TIA. The incidence of stroke or TIA appeared to increase in relation to the CHADS2 score [low (=1), 0 per 100 person-years; intermediate (=2), 1.6 per 100 person-years; high (≥3), 4.7 per 100 person-years; p = 0.04]. CHADS2 score could stratify the risk of ischemic stroke in CHF patients with the absence of AF, with greater prognostic power than the "stroke risk score".

Risk Stratification for Ventricular Tachyarrhythmias by Ambulatory Electrocardiogram-Based Frequency Domain T-Wave Alternans.

BACKGROUND: Ambulatory electrocardiogram (ECG)-based T-wave alternans (TWA) quantified by the modified moving average method (MMA) can be used to identify patients at risk for sudden cardiac death. However, there is no information available on ambulatory ECG-based TWA as quantified by the frequency domain (FD) method to identify patients with an implantable cardioverter defibrillator (ICD) who are at high risk for ventricular tachyarrhythmias. Further, there are few data regarding the comparison of clinical utility of FD-TWA with MMA-TWA, heart rate variability (HRV), and heart rate turbulence (HRT). METHODS AND RESULTS: In 41 patients with ICD, of whom 14 patients had a past history of at least one appropriate ICD discharge, FD-TWA, MMA-TWA, HRV, and HRT were analyzed from 24-hour Holter ECG monitoring recordings. Only positive results of FD-TWA and abnormal HRV (standard deviation of all normal-to-normal intervals ≤111 ms) were significantly more frequently observed in patients with than without appropriate ICD discharge. Patients with FD-TWA positive had a significantly higher risk of appropriate ICD discharge than those with FD-TWA negative (50% vs 16%; odds ratio, 5.3 [95% confidence interval, 1.2-23.7], P = 0.02). When FD-TWA and HRV were combined, the specificity (93% vs 59%, P = 0.003) and predictive accuracy (83% vs 66%, P = 0.07) for the identification of patients with appropriate ICD discharge were greater than those for FD-TWA only. CONCLUSION: The ambulatory ECG-based FD-TWA might be useful to detect patients with ICD who are at high risk for ventricular tachyarrhythmias, and the combination of FD-TWA and HRV might improve the ability to detect such high-risk patients.

Obstructive sleep apnea in Asian primary school children.

PURPOSE: The objectives of this study were to examine the prevalence of obstructive sleep apnea (OSA) in primary school children, relationships between OSA and tonsillar hypertrophy, adenoid, and patency of the nasal cavity, and the effects of the tonsillar hypertrophy and adenoid on the nasal patency. METHODS: An examination of the palatine tonsils and anterior rhinoscopy, completion of a questionnaire survey, a measurement of nasal resistance, an examination for sleep apnea at home using portable polysomnography device, and radiography of pharyngeal tonsil were performed in 152 primary school children. RESULTS: The obstructive apnea hypopnea index (O-AHI) increased with enlargements in the palatine tonsils. The adenoidal nasopharyngeal ratio (A/N ratio) decreased with advances in grade. A significant difference was observed in the O-AHI between those with and without adenoid. The median value of the O-AHI increased with advances in grade. The nasal resistance was significantly higher in the group with adenoid compared as in the group without. It was also higher in the nasal disease group with OSA than in the group without. Full polysomnography(PSG) was recommended in 16 (10.5%) of 152 who underwent the examination using the portable polysomnography device, and of the eight who underwent PSG, six (75%) were confirmed to have OSA, while its prevalence in all subjects was estimated as 7.9%. CONCLUSIONS: Disturbances in nasal respiration as well as tonsillar hypertrophy and adenoid were found to be a risk factor of OSA in primary school children.

Risk stratification by renal function and NYHA class in patients with hypotension initiated on sacubitril/valsartan: a retrospective cohort study from 17 centres in Japan.

BACKGROUND: Patients with heart failure exhibiting low systolic blood pressure (SBP) have a poor prognosis. Sacubitril/valsartan reduces cardiovascular events; however, its use in patients with low SBP has not been fully examined. Therefore, in this study, we aimed to investigate the association between baseline SBP and adverse events (AEs) in patients starting sacubitril/valsartan therapy using data from a real-world registry in Japan. METHODS: We analysed data from a multicentre retrospective study, including patients who initiated sacubitril/valsartan between August 2020 and August 2021. The patients were categorised into five groups based on their baseline SBP (<100, 100-109, 110-119, 120-129 and ≥130 mm Hg). The composite of AEs occurring within 3 months according to baseline SBP and the patient characteristics associated with AEs in a baseline SBP <110 mm Hg were analysed. RESULTS: Among the 964 patients newly prescribed sacubitril/valsartan, the median (IQR) age was 73 (61-80) years, and 388 (40.2%) patients had a baseline SBP <110 mm Hg. AEs occurred in 24% (n=232) of patients. The adjusted ORs for all AEs were 1.91 (95% CI (CI) 1.13-3.23; p=0.02) for the SBP <100 mm Hg group and 3.33 (95% CI 1.98 to 5.59; p<0.001) for the SBP 100-109 mm Hg group, compared with the SBP 110-119 mm Hg group. In patients with a baseline SBP <110 mm Hg, factors associated with an increased risk of AEs included a higher New York Heart Association class (II, III or IV) and a lower estimated glomerular filtration rate <30 mL/min/1.73 m2. CONCLUSIONS: Caution is needed when initiating sacubitril/valsartan in patients with lower baseline SBP. The severity of heart failure and kidney function may be useful for risk stratification in these high-risk patients.

The prognostic impact of follow-up cardiac metaiodobenzylguanidine imaging on left ventricular trajectory after acute decompensation.

AIMS: Cardiac metaiodobenzylguanidine (MIBG) imaging provides prognostic information in patients with heart failure (HF). Recently, the trajectory of left ventricular ejection fraction (LVEF) has been a focus in patients with reduced LVEF admitted for acute decompensated HF (ADHF). We sought to investigate the prognostic value of follow-up cardiac MIBG imaging in ADHF patients with reduced LVEF in relation to LVEF trajectory. METHODS AND RESULTS: We prospectively studied 145 ADHF patients with a reduced LVEF of <40%. The cardiac MIBG heart-to-mediastinum ratio (the late HMR) was measured on the delayed image at discharge and at the 6-month follow-up (6FUP). At 6 months after discharge, 54 (37%) patients had complete recovery of LVEF ≥50% (HFcorEF), and 43 (30%) patients had partial recovery of LVEF 40-50% (HFparEF), while the remaining 48 (33%) patients had no functional recovery of LVEF (HFnorEF). The late HMR at the 6FUP in HFcorEF patients was significantly greater than that in HFparEF and HFnorEF patients. During a follow-up period of 4.3 ± 2.6 years, 43 patients had cardiac events, defined as a composite of readmission for worsening HF and cardiac death. Patients with a lower late HMR at the 6FUP had a greater risk of cardiac events than those with a higher late HMR at the 6FUP in the group with recovered LVEF, especially HFparEF, which was not observed in the HFnorEF subgroup. CONCLUSION: Follow-up MIBG imaging after discharge could provide additional prognostic information in ADHF patients with recovered left ventricular function.

A Rare Case of a Common Inferior Pulmonary Vein Presumed to Be a Remnant of the Common Pulmonary Vein.

A 74-year-old woman with an implanted physiological DDD pacemaker visited our department complaining of palpitations due to atrial fibrillation (AF). Catheter ablation therapy for AF was scheduled. Preoperative multidetector computed tomography showed that the inferior pulmonary vein (PV) was a common trunk, and the left and right superior PVs branched from the center of the left atrial roof. In addition, mapping of the left atrium before AF ablation revealed no potential in either the inferior PV or common trunk. We performed left and right superior PV and posterior wall isolation. After ablation, AF was not observed on pacemaker recordings.

Impact of right ventricular and pulmonary vascular characteristics on Impella hemodynamic support in biventricular heart failure: A simulation study.

BACKGROUND: Impella (Abiomed, Danvers, MA, USA) is a percutaneous ventricular assist device commonly used in cardiogenic shock, providing robust hemodynamic support, improving the systemic circulation, and relieving pulmonary congestion. Maintaining adequate left ventricular (LV) filling is essential for optimal hemodynamic support by Impella. This study aimed to investigate the impact of pulmonary vascular resistance (PVR) and right ventricular (RV) function on Impella-supported hemodynamics in severe biventricular failure using cardiovascular simulation. METHODS: We used Simulink® (Mathworks, Inc., Natick, MA, USA) for the simulation, incorporating pump performance of Impella CP determined using a mock circulatory loop. Both systemic and pulmonary circulation were modeled using a 5-element resistance-capacitance network. The four cardiac chambers were represented by time-varying elastance with unidirectional valves. In the scenario of severe LV dysfunction (LV end-systolic elastance set at a low level of 0.4 mmHg/mL), we compared the changes in right (RAP) and left atrial pressures (LAP), total systemic flow, and pressure-volume loop relationship at varying degrees of RV function, PVR, and Impella flow rate. RESULTS: The simulation results showed that under low PVR conditions, an increase in Impella flow rate slightly reduced RAP and LAP and increased total systemic flow, regardless of RV function. Under moderate RV dysfunction and high PVR conditions, an increase in Impella flow rate elevated RAP and excessively reduced LAP to induce LV suction, which limited the increase in total systemic flow. CONCLUSIONS: PVR is the primary determinant of stable and effective Impella hemodynamic support in patients with severe biventricular failure.

The clinical relevance of mild cognitive impairment in acute heart failure: A comparison with cognitive impairment.

BACKGROUND: Although mild cognitive impairment (MCI) has received much attention as a precursor of dementia, its prognostic role has not been fully clarified in patients with heart failure (HF). METHODS AND RESULTS: We studied 274 patients admitted for acute decompensated HF. Cognitive function was evaluated using Mini Mental State Examination (MMSE). According to the previous definition, MMSE of 0-23, 24-27, and 28-30 were classified as CI (n = 132), MCI (n = 81), and normal cognitive function (n = 61). The primary endpoint was cardiac events, defined as the composite of unplanned HF hospitalization and cardiovascular mortality. During a mean follow-up period of 4.9 ±â€¯3.1 years, 145 patients experienced cardiac events. Multivariable logistic regression analysis showed that hypertension (p = 0.043), low cardiac index (p = 0.022), and low serum albumin level (p = 0.041) had a significant association with cognitive abnormalities. Both CI and MCI were significantly associated with cardiac events after Cox multivariable adjustment [CI: p = 0.001, adjusted HR 2.66 (1.48-4.77); MCI: p = 0.025, adjusted HR 1.90 (1.09-3.31), normal cognitive function group: reference]. Patients with MCI had a significantly higher risk of unplanned HF hospitalization [p = 0.033, adjusted HR 1.91 (1.05-3.47)], but not all-cause mortality (p = 0.533) or cardiovascular mortality (p = 0.920), while CI was significantly associated with all-cause mortality (p = 0.025) and cardiovascular mortality (p = 0.036). CONCLUSION: Even MCI had a significant risk of cardiac events in patients with acute decompensated HF. This risk was mainly derived from unplanned HF hospitalization.

Early repolarization pattern associated with sudden cardiac death: long-term follow-up in patients with chronic heart failure.

BACKGROUND: Identification of patients with chronic heart failure (CHF) at a risk for sudden cardiac death (SCD) is an important objective. Early repolarization pattern (ERP) is associated with ventricular fibrillation in patients without structural heart diseases. Moreover, ERP was reported to be associated with SCD in patients with old myocardial infarction in a case-control study. However, little information is available on the prognostic significance of ERP in CHF patients. Thus, we aimed to investigate whether ERP is associated with SCD in CHF patients. METHODS AND RESULTS: The study population consisted of 132 consecutive outpatients with NYHA class I, II and III congestive heart failure and radionuclide left ventricular ejection fraction less than 40%. All patients underwent the standard 12-lead electrocardiogram at enrollment, where we assessed the presence of ERP using the criteria of J-point elevation ≥ 0.1 mV in at least 2 inferior or lateral leads. The primary endpoint of this study was SCD. At enrollment, 16 patients had ERP. During the follow-up period of 6.7 ± 3.5 years, 26 patients had SCD. Kaplan-Meier analysis showed that SCD was observed significantly more frequently in patients with ERP than in those without ERP (63% [10/16] vs 14% [16/116], P < 0.0001]. A multivariate Cox analysis revealed that ERP was significantly and independently associated with SCD (hazard ratio, 3.7; 95% confidence interval, 1.6-8.6; P = 0.002). CONCLUSION: ERP in inferior leads would be associated with an increased risk of SCD in CHF patients.

Relevant adverse events and drug discontinuation of sacubitril/valsartan in a real-world Japanese cohort: REVIEW-HF registry.

BACKGROUND: The characteristics, tolerability, and outcomes in patients with heart failure (HF) who are treated with sacubitril/valsartan remain unclear in Japan. METHODS: We conducted a nationwide multicenter study to evaluate the features and outcomes of patients newly prescribed sacubitril/valsartan for the management of HF. We analyzed adverse events (AEs) related to sacubitril/valsartan at 3 months, which were defined as hypotension, worsening renal function, hyperkalemia, and angioedema. Additionally, the association between AEs and outcomes was examined. RESULTS: Among 993 patients, the mean age was 70 years and 291 (29.3 %) were female, and 22.8 % had left ventricular ejection fraction ≥50 %. Of them, 20.8 % had systolic blood pressure (sBP) <100 mmHg, and 19.5 % had estimated glomerular filtration rate (eGFR) <30 ml/min/1.73 m2 at baseline, which were the populations excluded from the eligibility in landmark trials. AEs related to sacubitril/valsartan were observed in 22.5 % of the patients at 3 months. Overall, 22.6 % of patients discontinued sacubitril/valsartan, and hypotension was the most common event leading to drug discontinuation. After adjustment, patients who had worse HF symptoms (New York Heart Association III or IV), sBP <100 mmHg, and eGFR <30 ml/min/1.73 m2 were associated with a higher risk of AEs related to sacubitril/valsartan. Additionally, patients experiencing AEs had a higher risk of cardiovascular death or HF hospitalization than those who did not. CONCLUSION: In Japan, sacubitril/valsartan was also prescribed to patients not eligible for landmark trials, and AEs were observed at a relatively high rate from soon after treatment initiation. Physicians should closely monitor patients for these events, especially in patients anticipated to have a higher risk of AEs.